Outcomes and performance of the ACURATE neo2 transcatheter heart valve in clinical practice: one-yearresults of the ACURATE neo2 PMCF Study.

BACKGROUND: Transcatheter aortic valve implantation is an effective treatment for patients with aortic stenosis; however, complications related to paravalvular leakage (PVL) persist, including increased risk of mortality, cardiovascular mortality, and rehospitalisation. AIMS: We sought to evaluate the clinical outcomes and valve performance at 1 year in patients with severe aortic stenosis treated with the ACURATE neo2 valve in a post-market clinical setting. METHODS: Valve Academic Research Consortium-2 safety events were assessed up to 1 year. Independent core laboratories evaluated echocardiographic measures of valve performance and hypoattenuated leaflet thickening (HALT; as measured by four-dimensional computed tomography). RESULTS: The study enrolled 250 patients (64% female; mean age: 81 years; baseline Society of Thoracic Surgeons risk score: 2.9±2.0%); 246 patients were implanted with ACURATE neo2. All-cause mortality was 0.8% at 30 days and 5.1% at 1 year. The 1-year rates for stroke and disabling stroke were 3.0% and 1.3%, respectively. Overall, HALT of >50% leaflet involvement of at least one leaflet was present in 9% of patients at 30 days and in 12% of patients at 1 year. No association was observed between the presence of HALT and 1-year clinical or haemodynamic outcomes. Early haemodynamic improvements were maintained up to 1 year (mean aortic valve gradient: 47.6±14.5 mmHg at baseline, 7.6±3.2 mmHg at 1 year; mean aortic valve area: 0.7±0.2 cm2 at baseline, 1.7±0.4 cm2 at 1 year). At 1 year, 99% of patients had mild or no/trace PVL (<1% had moderate PVL; no patient had severe PVL). CONCLUSIONS: The study outcomes confirm favourable performance and safety up to 1 year in patients treated with ACURATE neo2 in routine clinical practice. (ClinicalTrials.gov: NCT04655248).

Quantitative aortography for assessment of aortic regurgitation in the era of percutaneous aortic valve replacement.

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries.

First results from the ACURATE Prime XL human feasibility study.

BACKGROUND/PURPOSE: This prospective, open-label, single-arm study evaluated transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis with ACURATE Prime XL, an iteration of the ACURATE neo2 device designed with improved radial force and adaptations for compatibility with a larger annulus diameter (≥ 26.5 mm and ≤ 29 mm based on pre-procedure diagnostic imaging). METHODS: The composite primary device success endpoint was based on Valve Academic Research Consortium (VARC)-2 criteria. The primary safety endpoint was a composite of all-cause mortality and all stroke at 30 days. Aortic valve (AV) performance, including mean AV gradient, AV area, and grade of paravalvular leak (PVL), was assessed by an independent core laboratory. RESULTS: 13 male patients were enrolled at 3 Australian centers (mean age: 83.1 years; 10 of 13 were considered high/extreme operative risk). 61.5 % of patients met the primary device success endpoint. At 30 days, no patients experienced death or stroke; one patient received a permanent pacemaker. Mean AV gradient improved from baseline (42.7 ± 11.0 mmHg) to discharge (7.7 ± 2.5 mmHg) and through 30 days (7.2 ± 2.3 mmHg). Mean AV area was 0.8 ± 0.1 cm2 at baseline, 1.9 ± 0.3 cm2 at discharge, and 1.7 ± 0.3 cm2 at 30 days. Per core-laboratory adjudication, no patient had moderate or severe PVL at 30 days; 91.7 % had no/trace PVL and 8.3 % had mild PVL. CONCLUSIONS AND RELEVANCE: In this first-in-human feasibility study of the ACURATE Prime XL valve, there were no safety concerns, and no deaths or strokes within 30 days. Valve hemodynamics were favorable, and no patient had >mild PVL.

Effectiveness of Oral Hydration in Preventing Contrast-Induced Nephropathy in Individuals Undergoing Elective Coronary Interventions. / Eficácia da Hidratação Oral na Prevenção da Nefropatia Induzida por Contraste em Indivíduos Submetidos a Intervenções Coronárias Eletivas.

BACKGROUND: Contrast-induced nephropathy (CIN) is defined as worsening renal function, represented by an increase in serum creatinine of ≥ 25% or ≥ 0.5 mg/dL up to 72 h after exposure to iodinated contrast medium (ICM). The most effective preventive measure to date is intravenous hydration (IVH). Little is known about the effectiveness of outpatient oral hydration (OH). OBJETIVE: To investigate whether outpatient OH with water is as effective as IVH with 0.9% saline solution in preventing CIN in elective coronary procedures. METHODS: In this retrospective observational study, we analyzed the medical records and laboratory data of individuals undergoing percutaneous coronary procedures with ICM. Data collected between 2012 and 2015 refer to individuals who underwent IVH and those collected between 2016 and 2020 (after implementation of an OH protocol) correspond to individuals who underwent OH at home before and after coronary procedures as instructed by the nursing team. Statistical significance was established at α = 0.05. RESULTS: In total, 116 patients were included in this study: 58 in the IVH group and 58 in the OH group. An incidence of CIN of 15% (9/58) was observed in the group that received IVH and an incidence of 12% (7/58) was seen in the group that received OH (p = 0.68). CONCLUSION: The OH protocol, performed by the patient, appears to be as effective as the in-hospital IVH protocol for the renal protection of individuals susceptible to CIN in elective coronary interventions. These findings should be put to test in larger trials.

FUNDAMENTO: A nefropatia induzida por contraste (NIC) é definida como deterioração da função renal, representada por um aumento da creatinina sérica ≥25% ou ≥0,5 mg/dL até 72 horas após a exposição ao meio de contraste iodado (MCI). A medida preventiva mais eficaz até o momento é a hidratação venosa (HV). Pouco se sabe sobre a eficácia da hidratação oral (HO) ambulatorial. OBJETIVO: Investigar se a HO ambulatorial com água é tão eficaz quanto a HV com solução salina a 0,9% na prevenção de NIC em procedimentos coronarianos eletivos. MÉTODOS: Neste estudo observacional retrospectivo, foram analisados prontuários médicos e dados laboratoriais para coletar dados de indivíduos submetidos a procedimentos coronarianos percutâneos com MCI. Os dados coletados entre 2012 e 2015 avaliaram indivíduos que foram submetidos à HV e entre 2016 e 2020 (após a implementação de um protocolo de HO), os indivíduos que foram submetidos à HO em casa antes e depois de procedimentos coronarianos, conforme orientação da equipe de enfermagem. A significância estatística adotada foi de α=0,05. RESULTADOS: No total, 116 pacientes foram incluídos neste estudo, 58 no grupo HV e 58 no grupo HO. Observou-se incidência de NIC de 15% (9/58) no grupo que recebeu HV e 12% (7/58) no grupo que recebeu HO (p=0,68). CONCLUSÃO: O protocolo de HO realizado pelo paciente parece ser tão eficaz quanto o protocolo de HV hospitalar na proteção renal de indivíduos suscetíveis a desenvolver NIC em intervenções coronarianas eletivas. Essas descobertas devem ser testadas em ensaios mais abrangentes.

Eficácia da Hidratação Oral na Prevenção da Nefropatia Induzida por Contraste em Indivíduos Submetidos a Intervenções Coronárias Eletivas / Effectiveness of Oral Hydration in Preventing Contrast-Induced Nephropathy in Individuals Undergoing Elective Coronary Interventions

Resumo Fundamento A nefropatia induzida por contraste (NIC) é definida como deterioração da função renal, representada por um aumento da creatinina sérica ≥25% ou ≥0,5 mg/dL até 72 horas após a exposição ao meio de contraste iodado (MCI). A medida preventiva mais eficaz até o momento é a hidratação venosa (HV). Pouco se sabe sobre a eficácia da hidratação oral (HO) ambulatorial. Objetivo Investigar se a HO ambulatorial com água é tão eficaz quanto a HV com solução salina a 0,9% na prevenção de NIC em procedimentos coronarianos eletivos. Métodos Neste estudo observacional retrospectivo, foram analisados prontuários médicos e dados laboratoriais para coletar dados de indivíduos submetidos a procedimentos coronarianos percutâneos com MCI. Os dados coletados entre 2012 e 2015 avaliaram indivíduos que foram submetidos à HV e entre 2016 e 2020 (após a implementação de um protocolo de HO), os indivíduos que foram submetidos à HO em casa antes e depois de procedimentos coronarianos, conforme orientação da equipe de enfermagem. A significância estatística adotada foi de α=0,05. Resultados No total, 116 pacientes foram incluídos neste estudo, 58 no grupo HV e 58 no grupo HO. Observou-se incidência de NIC de 15% (9/58) no grupo que recebeu HV e 12% (7/58) no grupo que recebeu HO (p=0,68). Conclusão O protocolo de HO realizado pelo paciente parece ser tão eficaz quanto o protocolo de HV hospitalar na proteção renal de indivíduos suscetíveis a desenvolver NIC em intervenções coronarianas eletivas. Essas descobertas devem ser testadas em ensaios mais abrangentes.

Abstract Background Contrast-induced nephropathy (CIN) is defined as worsening renal function, represented by an increase in serum creatinine of ≥ 25% or ≥ 0.5 mg/dL up to 72 h after exposure to iodinated contrast medium (ICM). The most effective preventive measure to date is intravenous hydration (IVH). Little is known about the effectiveness of outpatient oral hydration (OH). Objetive To investigate whether outpatient OH with water is as effective as IVH with 0.9% saline solution in preventing CIN in elective coronary procedures. Methods In this retrospective observational study, we analyzed the medical records and laboratory data of individuals undergoing percutaneous coronary procedures with ICM. Data collected between 2012 and 2015 refer to individuals who underwent IVH and those collected between 2016 and 2020 (after implementation of an OH protocol) correspond to individuals who underwent OH at home before and after coronary procedures as instructed by the nursing team. Statistical significance was established at α = 0.05. Results In total, 116 patients were included in this study: 58 in the IVH group and 58 in the OH group. An incidence of CIN of 15% (9/58) was observed in the group that received IVH and an incidence of 12% (7/58) was seen in the group that received OH (p = 0.68). Conclusion The OH protocol, performed by the patient, appears to be as effective as the in-hospital IVH protocol for the renal protection of individuals susceptible to CIN in elective coronary interventions. These findings should be put to test in larger trials.

Clinical outcomes of the ACURATE neo2 transcatheter heart valve: a prospective, multicenter, observational, post-market surveillance study.

BACKGROUND: The next-generation ACURATE neo2 transcatheter aortic valve was designed for simplified implantation and to mitigate the risk of paravalvular leak (PVL) compared to the earlier device. AIMS: To collect clinical outcomes and device performance data, including echocardiography and 4-dimensional computed tomography (4D-CT) data, with the ACURATE neo2 transcatheter heart valve in patients with severe aortic stenosis (AS). METHODS: ACURATE neo2 PMCF is a single-arm, multicentre study of patients with severe AS treated in routine clinical practice. The primary safety endpoint was all-cause mortality at 30-days. The primary imaging endpoint was hypo-attenuated leaflet thickening (HALT), measured by core laboratory-adjudicated 4D-CT at 30 days. Secondary endpoints included VARC safety endpoints, procedural success, and evaluation of valve performance via core laboratory-adjudicated echocardiography. RESULTS: The study enrolled 250 patients at 18 European centres (mean age: 80.8 years; 63.6% female; mean STS score: 2.9±2.0%); 246 (98.4%) were successfully treated with ACURATE neo2. The 30-day rates for mortality and disabling stroke were 0.8% and 0%, respectively. The new permanent pacemaker implantation rate was 6.5%. HALT >50% was present in 9.3% of patients at 30 days. Valve haemodynamics improved from baseline to 30 days (mean aortic valve gradient: from 47.6±14.5 mmHg to 8.6±3.9 mmHg; mean aortic valve area: from 0.7±0.2 cm2 to 1.6±0.4 cm2). At 30 days, PVL was evaluated as none/trace in 79.2% of patients, mild in 18.9%, moderate in 1.9%, and severe in 0%. CONCLUSIONS: The study results support the safety and efficacy of TAVI with ACURATE neo2 in patients in routine clinical practice.

Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke. METHODS: We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR. RESULTS: A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site. CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

Impact of coronary calcification assessed by coronary CT angiography on treatment decision in patients with three-vessel CAD: insights from SYNTAX III trial.

OBJECTIVES: The aim of this study was to determine Syntax scores based on coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) and to assess whether heavy coronary calcification significantly limits the CCTA evaluation and the impact of severe calcification on heart team's treatment decision and procedural planning in patients with three-vessel coronary artery disease (CAD) with or without left main disease. METHODS: SYNTAX III was a multicentre, international study that included patients with three-vessel CAD with or without left main disease. The heart teams were randomized to either assess coronary arteries with coronary CCTA or ICA. We stratified the patients based on the presence of at least 1 lesion with heavy calcification defined as arc of calcium >180° within the lesion using CCTA. Agreement on the anatomical SYNTAX score and treatment decision was compared between patients with and without heavy calcifications. RESULTS: Overall, 222 patients with available CCTA and ICA were included in this trial subanalysis (104 with heavy calcification, 118 without heavy calcification). The mean difference in the anatomical SYNTAX score (CCTA derived-ICA derived) was lower in patients without heavy calcifications [mean (-1.96 SD; +1.96 SD) = 1.5 (-19.3; 22.4) vs 5.9 (-17.5; +29.3), P = 0.004]. The agreement on treatment decision did not differ between patients with (Cohen's kappa 0.79) or without coronary calcifications (Cohen's kappa 0.84). The agreement on the treatment planning did not differ between patients with (concordance 80.3%) or without coronary calcifications (concordance 82.8%). CONCLUSIONS: An overall good correlation between CCTA- and ICA-derived Syntax score was found. The presence of heavy coronary calcification moderately influenced the agreement between CCTA and ICA on the anatomical SYNTAX score. However, agreement on the treatment decision and planning was high and irrespective of the presence of calcified lesions.

Validation of Prosthetic Mitral Regurgitation Quantification Using Novel Angiographic Platform by Mock Circulation.

OBJECTIVES: This study aimed to validate a dedicated software for quantitative videodensitometric angiographic assessment of mitral regurgitation (QMR). BACKGROUND: Quantitative videodensitometric aortography of aortic regurgitation using the time-density principle is a well-documented technique, but the angiographic assessment of mitral regurgitation (MR) remains at best semi-quantitative and operator dependent. METHODS: Fourteen sheep underwent surgical mitral valve replacement using 2 different prostheses. Pre-sacrifice left ventriculograms were used to assess MR fraction (MRF) using QMR and MR volume (MRV). In an independent core lab, the CAAS QMR 0.1 was used for QMR analysis. In vitro MRF and MRV were assessed in a mock circulation at a comparable cardiac output to the in vivo one by thermodilution. The correlations and agreements of in vitro and in vivo MRF, MRV, and interobserver reproducibility for QMR analysis were assessed using the averaged cardiac cycles (CCs). RESULTS: In vivo derived MRF by QMR strongly correlated with in vitro derived MRF, regardless of the number of the CCs analyzed (best correlation: 3 CCs y = 0.446 + 0.994x; R = 0.784; p =0.002). The mean absolute difference between in vitro derived MRF and in vivo derived MRF from 3 CCs was 0.01 ± 4.2% on Bland-Altman analysis. In vitro MRV and in vivo MRV from 3 CCs were very strongly correlated (y = 0.196 + 1.255x; R = 0.839; p < 0.001). The mean absolute difference between in vitro MRV and in vivo MRV from 3 CCs was -1.4 ± 1.9 ml. There were very strong correlations of in vivo MRF between 2 independent analysts, regardless of the number of the CCs. CONCLUSIONS: In vivo MRF using the novel software is feasible, accurate, and highly reproducible. These promising results have led us to initiate the first human feasibility study comprising patients undergoing percutaneous mitral valve edge-to-edge repair.

Chronic haemodynamic performance of a biorestorative transcatheter heart valve in an ovine model.

BACKGROUND: The Xeltis biorestorative transcatheter heart valve (BTHV) leaflets are made from an electrospun bioabsorbable supramolecular polycarbonate-urethane and are mounted on a self-expanding nitinol frame. The acute haemodynamic performance of this BTHV was favourable. AIMS: We sought to demonstrate the preclinical feasibility of a novel BTHV by evaluating the haemodynamic performances of five pilot valve designs up to 12 months in a chronic ovine model. METHODS: Five design iterations (A, B, B', C, and D) of the BTHV were transapically implanted in 46 sheep; chronic data were available in 39 animals. Assessments were performed at implantation, 3, 6, and 12 months including quantitative aortography, echocardiography, and histology. RESULTS: At 12 months, greater than or equal to moderate AR on echocardiography was seen in 0%, 100%, 33.3%, 100%, and 0% in the iterations A, B, B', C, and D, respectively. Furthermore, transprosthetic mean gradients on echocardiography were 10.0±2.8 mmHg, 19.0±1.0 mmHg, 8.0±1.7 mmHg, 26.8±2.4 mmHg, and 11.2±4.1 mmHg, and effective orifice area was 0.7±0.3 cm2, 1.1±0.3 cm2, 1.5±1.0 cm2, 1.5±0.6 cm2, and 1.0±0.4 cm2 in the iterations A, B, B', C, and D, respectively. On pathological evaluation, the iteration D demonstrated generally intact leaflets and advanced tissue coverage, while different degrees of structural deterioration were observed in the other design iterations. CONCLUSIONS: Several leaflet material iterations were compared for the potential to demonstrate endogenous tissue restoration in an aortic valve in vivo. The most promising iteration showed intact leaflets and acceptable haemodynamic performance at 12 months, illustrating the potential of the BTHV.

Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. / Efeitos da Terapia com Anti-TNF alfa na Pressão Arterial em Pacientes com Hipertensão Resistente: Um Estudo Piloto Randomizado, Duplo-Cego e Controlado por Placebo.

BACKGROUND: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown. OBJECTIVE: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects. METHODS: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05. RESULTS: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol. CONCLUSIONS: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451).

FUNDAMENTO: A citocina fator de necrose tumoral alfa (TNF-α) é elevada na hipertensão resistente (HAR), mas os efeitos dos inibidores de TNF-α nessa população ainda são desconhecidos. OBJETIVOS: O objetivo deste estudo foi avaliar se uma única dose de infliximabe controlada por placebo reduz a pressão arterial (PA) de forma aguda em pacientes com HAR. MÉTODOS: Realizamos um estudo cruzado, randomizado, duplo-cego e controlado por placebo em que pacientes com HAR receberam infliximabe ou placebo. O desfecho primário foi a alteração dos níveis de PA média em relação ao basal imediatamente após a infusão, obtida por avaliação hemodinâmica não invasiva contínua, batimento a batimento. Os desfechos secundários incluíram alterações em medidas de PA central, ambulatorial e em consultório, na função endotelial, e nos biomarcadores inflamatórios após 7 dias. O nível de significância aceito foi alfa=0,05. RESULTADOS: Foram incluídos dez portadores de HAR. O resultado do desfecho primário demonstrou uma redução aguda dos níveis de PA média (média das diferenças ± desvio padrão = -6,3 ± 7,2 mmHg, p=0,02) em relação ao basal, após o uso de infliximabe, em comparação com o placebo. Os níveis de PA diastólica (-4,9 ± 5,5 mmHg, p=0,02), mas não os níveis de PA sistólica (-9,4 ± 19,7 mmHg, p=0,16), reduziram após a infusão de infliximabe. Não foram identificadas diferenças significativas nos demais parâmetros hemodinâmicos, nem nos resultados dos desfechos secundários, com exceção dos níveis de TNF-α, que aumentaram continuamente após o uso de infliximabe. Não foram relatados eventos adversos durante o protocolo. CONCLUSÕES: Uma dose única de infliximabe reduziu os níveis de PA média e diastólica imediatamente após sua infusão, em comparação com placebo em HAR. A terapia com anti-TNF-α foi considerada segura e bem tolerada. Os resultados desse estudo prova de conceito são geradores de hipótese e precisam ser investigados em maior detalhe. (Arq Bras Cardiol. 2021; 116(3):443-451).

Gensini Score and Thrombus Burden Add Predictive Value to the SYNTAX Score in Detecting No-Reflow after Myocardial Infarction. / O Escore Gensini e a Carga Trombótica Adicionam Valor Preditivo ao Escore SYNTAX na Detecção de No-Reflow após Infarto do Miocárdio.

BACKGROUND: No-reflow after percutaneous coronary intervention is associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). SYNTAX score is a good predictor of no-reflow. OBJECTIVE: We aimed to evaluate whether atherosclerotic burden (Gensini score) and thrombus burden in the culprit coronary artery would improve the ability of the SYNTAX score to detect no-reflow. METHODS: In this prospective cohort study, consecutive patients with STEMI who presented within 12 h of onset of symptoms were selected for this study. No-reflow was defined as TIMI flow < 3 o r TIMI flow = 3 but myocardial blush grade <2. Thrombus burden was quantified according to the TIMI thrombus grade scale (0 to 5). RESULTS: A total of 481 patients were included (mean age 61±11 years). No-reflow occurred in 32.8%. SYNTAX score (OR=1.05, 95%CI 1.01-1.08, p<0.01), thrombus burden (OR=1.17, 95%CI 1.06-1.31, p<0.01), and Gensini score (OR=1.37, 95%CI 1.13-1.65, p<0.01) were independent predictors of no-reflow. Combined scores had a larger area under the curve than the SYNTAX score alone (0.78 [0.73-0.82] vs 0.73 [0.68-0.78], p=0.03). Analyses of both categorical (0.11 [0.01-0.22], p=0.02), and continuous net reclassification improvement (NRI>0) (0.54 [0.035-0.73], p<0.001) showed improvement in the predictive ability of no-reflow in the combined model, with integrated discrimination improvement (IDI) of 0.07 (0.04-0.09, p<0.001). CONCLUSIONS: Our findings suggest that, in patients with STEMI undergoing percutaneous coronary intervention, atherosclerotic burden and thrombus burden in the culprit artery add predictive value to the SYNTAX score in detecting the no-reflow phenomenon. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0).

FUNDAMENTO: O fenômeno de no-reflow após a intervenção coronária percutânea está associado a um pior prognóstico em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). O escore SYNTAX é um bom preditor de no-reflow. OBJETIVO: Nosso objetivo foi avaliar se a carga aterosclerótica (escore Gensini) e a carga trombótica na artéria coronária culpada melhorariam a capacidade do escore SYNTAX para detectar o no-reflow. MÉTODOS: Neste estudo coorte prospectivo, foram estudados pacientes com IAMCSST consecutivos que se apresentaram dentro de 12 horas a partir do início dos sintomas. O no-reflow foi definido como fluxo TIMI < 3 ou fluxo TIMI =3 mas grau de blush miocárdico (myocardial blush grade) < 2. A carga trombótica foi quantificada de acordo com o grau TIMI de trombo (0 a 5). RESULTADOS: Foram incluídos 481 pacientes no estudo, com idade média de 61±11 anos. O fenômeno de no-reflow ocorreu em 32,8% dos pacientes. O escore SYNTAX (OR=1,05, IC95% 1,01­1,08, p<0,01), a carga trombótica (OR=1,17, IC95% 1,06­1,31, p<0,01), e o escore Gensini (OR=1,37, IC95% 1,13­1,65, p<0,01) foram preditores independentes do no-reflow. Os escores combinados apresentaram uma maior área sob a curva quando comparados ao escore SYNTAX isolado (0,78 [0,73­0,82] vs 0,73 [0,68­0,78], p=0,03). A análise da melhora da reclassificação líquida (NRI) categórica (0,11 [0,01­0,22], p=0,02) e contínua (NRI>0) (0,54 [0,035­0,73], p<0.001) mostrou melhora na capacidade preditiva do no-reflow no modelo combinado, com melhora da discriminação integrada (IDI) de 0,07 (0,04­0,09, p<0,001). CONCLUSÕES: Nossos achados sugerem que, em pacientes com IAMCSST submetidos à intervenção coronária percutânea, a carga aterosclerótica e a carga trombótica na artéria culpada adicionam valor preditivo ao escore SYNTAX na detecção do fenômeno no-reflow. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0).

Serum potassium levels provide prognostic information in symptomatic heart failure beyond traditional clinical variables.

AIMS: Despite of recent advances in the pharmacological treatment, heart failure (HF) maintains significant morbidity and mortality rates. While serum potassium disorders are common and associated with adverse outcomes, the exact recommended potassium level for patients with HF are not entirely established. We aimed to investigate the prognostic role of potassium levels on a cohort of patients with symptomatic chronic HF. METHODS AND RESULTS: Patients with symptomatic chronic HF were identified at the referral to 6 min walking test (6MWT) and were prospectively followed up for cardiovascular events. Clinical and laboratorial data were retrospectively obtained. The primary endpoint was the composite of cardiovascular death, hospitalization due to HF, and heart transplantation. The cohort included 178 patients with HF with the mean age of 51 ± 12.76 years, 39% were female, 85% of non-ischaemic cardiomyopathy, and 38% had New York Heart Association Class III with a relatively high Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score (12.91 ± 6.6). The mean left ventricular ejection fraction was 39.98 ± 15.79%, and the mean 6MWT distance was 353 ± 136 m. After a median follow-up of 516 days, there were 22 major cardiovascular events (4 cardiovascular deaths, 13 HF admissions, and 5 heart transplants). Patients were stratified according to cut-point level of serum potassium of 4.7 mmol/L to predict combined cardiac events based on receiver operating characteristic analysis. Individuals with higher potassium levels had worse renal function (glomerular filtration rate, K ≤ 4.7: 102.8 ± 32.2 mL/min/1.73 m2 vs. K > 4.7: 85.42 ± 36.2 mL/min/1.73 m2 , P = 0.004), higher proportion of New York Heart Association Class III patients (K ≤ 4.7: 28% vs. K > 4.7: 48%, P = 0.0029), and also higher MAGGIC score (K ≤ 4.7: 12.08 ± 5.7 vs. K > 4.7: 14.9 ± 7.9, P = 0.0089), without significant differences on the baseline pharmacological HF treatment. Both potassium levels [hazard ratio (HR) 4.26, 95% confidence interval (CI) 1.59-11.421, P = 0.003] and 6MWT distance (HR 0.99, 95% CI 0.993-0.999, P = 0.01) were independently associated with the primary outcome. After adjustments for MAGGIC score and 6MWT distance, potassium levels > 4.7 mmol/L maintained a significant association with outcomes (HR 3.57, 95% CI 1.305-9.807, P = 0.013). Patients with K > 4.7 mmol/L were more likely to present clinical events during the follow-up (log rank = 0.005). Adding potassium levels to the model including 6MWT and MAGGIC significantly improved the prediction of events over 2 years (integrated discrimination index 0.105, 95% CI 0.018-0.281, P = 0.012 and net reclassification index 0.447, 95% CI 0.077-0.703, P = 0.028). CONCLUSIONS: Potassium levels were independently associated with worse outcomes in patients with chronic symptomatic HF, also improving the accuracy model for prognostic prediction when added to MAGGIC score and 6MWT distance. The potassium levels above 4.7 mmol/L might identify those patients at an increased risk of cardiovascular events.

Efeitos da Terapia com Anti-TNF alfa na Pressão Arterial em Pacientes com Hipertensão Resistente: Um Estudo Piloto Randomizado, Duplo-Cego e Controlado por Placebo / Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Resumo Fundamento: A citocina fator de necrose tumoral alfa (TNF-α) é elevada na hipertensão resistente (HAR), mas os efeitos dos inibidores de TNF-α nessa população ainda são desconhecidos. Objetivos: O objetivo deste estudo foi avaliar se uma única dose de infliximabe controlada por placebo reduz a pressão arterial (PA) de forma aguda em pacientes com HAR. Métodos: Realizamos um estudo cruzado, randomizado, duplo-cego e controlado por placebo em que pacientes com HAR receberam infliximabe ou placebo. O desfecho primário foi a alteração dos níveis de PA média em relação ao basal imediatamente após a infusão, obtida por avaliação hemodinâmica não invasiva contínua, batimento a batimento. Os desfechos secundários incluíram alterações em medidas de PA central, ambulatorial e em consultório, na função endotelial, e nos biomarcadores inflamatórios após 7 dias. O nível de significância aceito foi alfa=0,05. Resultados: Foram incluídos dez portadores de HAR. O resultado do desfecho primário demonstrou uma redução aguda dos níveis de PA média (média das diferenças ± desvio padrão = -6,3 ± 7,2 mmHg, p=0,02) em relação ao basal, após o uso de infliximabe, em comparação com o placebo. Os níveis de PA diastólica (-4,9 ± 5,5 mmHg, p=0,02), mas não os níveis de PA sistólica (-9,4 ± 19,7 mmHg, p=0,16), reduziram após a infusão de infliximabe. Não foram identificadas diferenças significativas nos demais parâmetros hemodinâmicos, nem nos resultados dos desfechos secundários, com exceção dos níveis de TNF-α, que aumentaram continuamente após o uso de infliximabe. Não foram relatados eventos adversos durante o protocolo. Conclusões: Uma dose única de infliximabe reduziu os níveis de PA média e diastólica imediatamente após sua infusão, em comparação com placebo em HAR. A terapia com anti-TNF-α foi considerada segura e bem tolerada. Os resultados desse estudo prova de conceito são geradores de hipótese e precisam ser investigados em maior detalhe. (Arq Bras Cardiol. 2021; 116(3):443-451)

Abstract Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown. Objective: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects. Methods: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05. Results: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol. Conclusions: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451)

O Escore Gensini e a Carga Trombótica Adicionam Valor Preditivo ao Escore SYNTAX na Detecção de No-Reflow após Infarto do Miocárdio / Gensini Score and Thrombus Burden Add Predictive Value to the SYNTAX Score in Detecting No-Reflow after Myocardial Infarction

Resumo Fundamento O fenômeno de no-reflow após a intervenção coronária percutânea está associado a um pior prognóstico em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). O escore SYNTAX é um bom preditor de no-reflow. Objetivo Nosso objetivo foi avaliar se a carga aterosclerótica (escore Gensini) e a carga trombótica na artéria coronária culpada melhorariam a capacidade do escore SYNTAX para detectar o no-reflow. Métodos Neste estudo coorte prospectivo, foram estudados pacientes com IAMCSST consecutivos que se apresentaram dentro de 12 horas a partir do início dos sintomas. O no-reflow foi definido como fluxo TIMI < 3 ou fluxo TIMI =3 mas grau de blush miocárdico (myocardial blush grade) < 2. A carga trombótica foi quantificada de acordo com o grau TIMI de trombo (0 a 5). Resultados Foram incluídos 481 pacientes no estudo, com idade média de 61±11 anos. O fenômeno de no-reflow ocorreu em 32,8% dos pacientes. O escore SYNTAX (OR=1,05, IC95% 1,01-1,08, p<0,01), a carga trombótica (OR=1,17, IC95% 1,06-1,31, p<0,01), e o escore Gensini (OR=1,37, IC95% 1,13-1,65, p<0,01) foram preditores independentes do no-reflow. Os escores combinados apresentaram uma maior área sob a curva quando comparados ao escore SYNTAX isolado (0,78 [0,73-0,82] vs 0,73 [0,68-0,78], p=0,03). A análise da melhora da reclassificação líquida (NRI) categórica (0,11 [0,01-0,22], p=0,02) e contínua (NRI>0) (0,54 [0,035-0,73], p<0.001) mostrou melhora na capacidade preditiva do no-reflow no modelo combinado, com melhora da discriminação integrada (IDI) de 0,07 (0,04-0,09, p<0,001). Conclusões Nossos achados sugerem que, em pacientes com IAMCSST submetidos à intervenção coronária percutânea, a carga aterosclerótica e a carga trombótica na artéria culpada adicionam valor preditivo ao escore SYNTAX na detecção do fenômeno no-reflow. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Abstract Background No-reflow after percutaneous coronary intervention is associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). SYNTAX score is a good predictor of no-reflow. Objective We aimed to evaluate whether atherosclerotic burden (Gensini score) and thrombus burden in the culprit coronary artery would improve the ability of the SYNTAX score to detect no-reflow. Methods In this prospective cohort study, consecutive patients with STEMI who presented within 12 h of onset of symptoms were selected for this study. No-reflow was defined as TIMI flow < 3 o r TIMI flow = 3 but myocardial blush grade <2. Thrombus burden was quantified according to the TIMI thrombus grade scale (0 to 5). Results A total of 481 patients were included (mean age 61±11 years). No-reflow occurred in 32.8%. SYNTAX score (OR=1.05, 95%CI 1.01-1.08, p<0.01), thrombus burden (OR=1.17, 95%CI 1.06-1.31, p<0.01), and Gensini score (OR=1.37, 95%CI 1.13-1.65, p<0.01) were independent predictors of no-reflow. Combined scores had a larger area under the curve than the SYNTAX score alone (0.78 [0.73-0.82] vs 0.73 [0.68-0.78], p=0.03). Analyses of both categorical (0.11 [0.01-0.22], p=0.02), and continuous net reclassification improvement (NRI>0) (0.54 [0.035-0.73], p<0.001) showed improvement in the predictive ability of no-reflow in the combined model, with integrated discrimination improvement (IDI) of 0.07 (0.04-0.09, p<0.001). Conclusions Our findings suggest that, in patients with STEMI undergoing percutaneous coronary intervention, atherosclerotic burden and thrombus burden in the culprit artery add predictive value to the SYNTAX score in detecting the no-reflow phenomenon. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Online Quantitative Aortographic Assessment of Aortic Regurgitation After TAVR: Results of the OVAL Study.

OBJECTIVES: The aim of this study was to investigate the online assessment feasibility of aortography using videodensitometry in the catheterization laboratory during transcatheter aortic valve replacement (TAVR). BACKGROUND: Quantitative assessment of regurgitation after TAVR through aortography using videodensitometry is simple, reproducible, and validated in vitro, in vivo, in clinical trials, and in "real-world" patients. However, thus far the assessment has been done offline. METHODS: This was a single center, prospective, proof-of-principle, feasibility study. One hundred consecutive patients with aortic stenosis and indications to undergo TAVR were enrolled. All final aortograms were analyzed immediately after acquisition in the catheterization laboratory and were also sent to an independent core laboratory for blinded offline assessment. The primary endpoint of the study was the feasibility of the online assessment of regurgitation (percentage of analyzable cases). The secondary endpoint was the reproducibility of results between the online assessment and the offline analysis by the core laboratory. RESULTS: Patients' mean age was 81 ± 7 years, and 56% were men. The implanted valves were either SAPIEN 3 (97%) or SAPIEN 3 Ultra (3%). The primary endpoint of online feasibility of analysis was 92% (95% confidence interval [CI]: 86% to 97%) which was the same feasibility encountered by the core laboratory (92%; 95% CI: 86% to 97%). Reproducibility assessment showed a high correlation between online and core laboratory evaluations (R2 = 0.87, p < 0.001), with an intraclass correlation coefficient of 0.962 (95% CI: 0.942 to 0.975; p < 0.001). CONCLUSIONS: This study showed high feasibility of online quantitative assessment of regurgitation and high agreement between the online examiner and core laboratory. These results may pave the way for the application of videodensitometry in the catheterization laboratory after TAVR. (Online Videodensitometric Assessment of Aortic Regurgitation in the Cath-Lab [OVAL]; NCT04047082).